Clinicopathologic Characteristics of Pediatric Follicular Variant of Papillary Thyroid Carcinoma Subtypes: A Retrospective Cohort Study.

Introduction: Follicular patterned thyroid nodules with nuclear features of papillary thyroid carcinoma (PTC) encompass a range of diagnostic categories with varying risks of metastatic behavior. Subtypes include the invasive encapsulated follicular variant of PTC (Ienc-fvPTC) and infiltrative fvPTC (inf-fvPTC), with tumors lacking invasive features classified as noninvasive follicular thyroid neoplasms with papillary-like features (NIFTPs). This study aimed to report the clinical and histological features of pediatric cases meeting criteria for these histological subtypes, with specific focus on Ienc-fvPTC and inf-fvPTC. Methods: In this retrospective cohort study, pediatric patients with thyroid neoplasms showing follicular patterned growth and nuclear features of PTC noted on surgical pathology between January 2010 and January 2021 were retrospectively reviewed and classified according to the recent 2022 World Health Organization (WHO) criteria. Clinical and histopathologic parameters were described for NIFTP, Ienc-fvPTC, and inf-fvPTC subtypes, with specific comparison of Ienc-fvPTC and inf-fvPTC cases. Results: The case cohort included 42 pediatric patients, with 6 (14%), 25 (60%), and 11 (26%) patients meeting criteria for NIFTP, Ienc-fvPTC, and inf-fvPTC, respectively. All cases were rereviewed, and 5 patients originally diagnosed with Ienc-fvPTC before 2017 were reappraised as having NIFTPs. The NIFTP cases were encapsulated tumors without invasive features, lymph node or distant metastasis, or disease recurrence. Ienc-fvPTC tumors demonstrated clearly demarcated tumor capsules and capsular/vascular invasion, while inf-fvPTC tumors displayed infiltrative growth lacking a capsule. inf-fvPTC cases had increased prevalence of malignant preoperative cytology, lymph node metastasis, and distant metastasis (p < 0.01). These cases were treated with total thyroidectomy, lymph node dissection, and subsequent radioactive iodine therapy. Preliminary genetic findings suggest a predominance of fusions in inf-fvPTC cases versus point mutations in Ienc-fvPTC (p = 0.02). Conclusions: Pediatric NIFTP and fvPTC subtypes appear to demonstrate alignment between clinical and histological risk stratification, with indolent behavior in Ienc-fvPTC and invasive features in inf-fvPTC tumors.

Breast metastasis of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and regional neck metastasis is more common than distant metastasis. If present, metastasis most frequently occurs in lungs and bones. Follicular variant of papillary thyroid carcinoma (FVPTC) is a mixture of the classic and follicular thyroid carcinoma and metastasizes in the same fashion as the PTC with cervical lymph nodes as the most common site. A case of atypical presentation of FVPTC with rib metastasis is reported. We present a case of an old man with a left-sided palpable breast mass for 2 months in duration without breast pain. Initially, the breast mass was categorised as Breast Imaging Reporting and Data System (BI-RADS) 4a via ultrasonography. Subsequent immunohistochemistry demonstrated that the mass was metastatic thyroid cancer. Consequently, a CT scan revealed a tumour originating from the rib. The patient was finally diagnosed with metastatic FVPTC.

Carcinoma papilar tiroideo con invasión locorregional: reporte de caso / Papillary thyroid crcinoma with locoregional invasion: case report

El cáncer diferenciado de tiroides incluye el tipo papilar y folicular que representan más del 80% de los casos y tienen un excelente pronóstico. Existen varios subtipos histológicos y las variantes foliculares son probablemente las más comunes. La incidencia de cáncer papilar variante folicular ha ido en aumento. En un reporte de un solo centro, cerca del 40% de los cánceres papilares eran variantes foliculares1. El subtipo infiltrativo de la variante folicular presenta sectores que invaden el parénquima tiroideo no neoplásico y carece de una cápsula tumoral bien definida. Tiene un comportamiento biológico y un perfil molecular que es más similar al tumor papilar clásico2. Existen características clínicas y patológicas asociadas con riesgo más alto de recurrencia tumoral y mortalidad; entre ellos se describen el tamaño del tumor primario y la presencia de invasión de tejidos blandos3. En la invasión de estructuras adyacentes, los sitios más comprometidos incluyen los músculos pretiroideos, el nervio laríngeo recurrente, el esófago, la faringe, laringe y la tráquea. Además, puede haber otras estructuras involucradas como: la vena yugular interna, la arteria carótida y los nervios vago, frénico y espinal4. El compromiso de los ganglios linfáticos y la incidencia de metástasis ganglionares en adultos depende de la extensión de la cirugía. Entre los que se realizan una disección radical modificada del cuello, hasta el 80% tienen metástasis en los ganglios linfáticos y el 50% de ellas son microscópicas5. Clínicamente los tumores localmente avanzados cursan con disfonía, disfagia, disnea, tos o hemoptisis, pero la ausencia de síntomas no descarta la invasión local. Según las guías de la American Thyroid Association6 son variables de mal pronóstico: la edad del paciente, el tamaño del tumor primario, la extensión extra tiroidea y la resección quirúrgica incompleta.

Differentiated thyroid cancer includes papillary and follicular types that represent more than 80% of cases and have an excellent prognosis. There are several histologic subtypes, and follicular variants are probably the most common. The incidence of papillary follicular variant cancer has been increasing. In a singlecenter report, about 40% of papillary cancers were follicular variants1. The infiltrative subtype of the follicular variant presents sectors that invade the non-neoplastic thyroid parenchyma and lacks a well-defined tumor capsule. It has a biological behavior and a molecular profile that is more similar to the classic papillary tumor2. There are clinical and pathological characteristics associated with a higher risk of tumor recurrence and mortality; These include the size of the primary tumor and the presence of soft tissue invasion3. In the invasion of adjacent structures, the most compromised sites include the pre-thyroid muscles, the recurrent laryngeal nerve, the esophagus, the pharynx, larynx and trachea. In addition, there may be other structures involved such as: the internal jugular vein, the carotid artery and the vagus, phrenic and spinal nerves4. The involvement of the lymph nodes and the incidence of lymph node metastases in adults depends on the extent of the surgery. Among those who undergo a modified radical neck dissection, up to 80% have lymph node metastases and 50% of them are microscopic5. Clinically locally advanced tumors present with dysphonia, dysphagia, dyspnea, cough, or hemoptysis, but the absence of symptoms does not rule out local invasion. According to the American Thyroid Association guidelines6, there are variables with a poor prognosis: the age of the patient, the size of the primary tumor, the extra-thyroid extension, and incomplete surgical resection.

High Incidence of Distant Metastasis Is Associated With Histopathological Subtype of Pediatric Papillary Thyroid Cancer - a Retrospective Analysis Based on SEER.

Objective: Children with papillary thyroid cancer (PTC) have a higher invasive rate and distant metastasis rate, but the mortality rate is lower with unknown reasons. The majority of PTC cases comprise classical papillary thyroid carcinoma (CPTC) and follicular variant papillary thyroid carcinoma (FVPTC). This study aimed to determine the relationship between histopathological subtype and rate of distant metastasis and investigate factors influencing distant metastasis in pediatric PTC. Methods: A total of 102,981 PTC patients were recruited from SEER registry, 2004-2015. Proportion of distant metastasis between children (≤18 years) and adults with different histopathological subtypes was compared by propensity score matching. The cut-off age for distant metastasis in children was calculated by receiver operating characteristic (ROC) curve, and the risk factors for distant metastasis in pediatric patients were analyzed by logistic regression models. Results: Among the 1,484 children and 101,497 adults included in the study, the incidence of CPTC patients with distant metastasis in children was higher than that in adults (p<0.001). The ROC curve was calculated, which yielded a cut-off age for distant metastasis in CPTC children as 16 years old. In CPTC, the proportion of young children (2-16 years) with distant metastasis was higher than that of adolescents (17-18 years) and adults (>18 years) (both p<0.001). While there was no such trend in FVPTC. In young children (2-16 years), the incidence of CPTC with distant metastasis was higher than FVPTC (p=0.006). There was no difference between the proportion of CPTC and FVPTC with distant metastasis in adolescents (17-18 years) and adults. Logistic regression models revealed that extrathyroidal extension, lymph node metastasis and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2 -16 years. Conclusions: In CPTC, the incidence of distant metastasis in young children (2-16 years) was significantly higher than that in adolescents (17-18 years) and adults (>18 years). In patients with distant metastasis aged 2-16 years, the proportion of CPTC was higer than that of FVPTC. Extrathyroidal extension, lymph node metastasis, and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2-16 years.

Whole Tumor Capsule Is Prognostic of Very Good Outcome in the Classical Variant of Papillary Thyroid Cancer.

CONTEXT: Tumor capsule integrity is becoming a relevant issue to predict the biological behavior of human tumors, including thyroid cancer. OBJECTIVE: This work aims to verify whether a whole tumor capsule in the classical variant of papillary thyroid carcinoma (CVPTC) could have as a predictive role of a good outcome as for follicular variant (FVPTC). METHODS: FVPTC (n = 600) and CVPTC (n = 554) cases were analyzed. We distinguished between encapsulated-FVPTC (E-FVPTC) and encapsulated-CVPTC (E-CVPTC) and, thereafter, invasive (Ei-FVPTC and Ei-CVPTC) and noninvasive (En-FVPTC and En-CVPTC) tumors, according to the invasion or integrity of the tumor capsule, respectively. Cases without a tumor capsule were indicated as invasive-FVPTC (I-FVPTC) and invasive-CVPTC (I-CVPTC). The subgroup of each variant was evaluated for BRAF mutations. RESULTS: E-FVPTC was more frequent than E-CVPTC (P < .001). No differences were found between En-FVPTC and En-CVPTC or between Ei-FVPTC and Ei-CVPTC. After 18 years of follow-up, a greater number of not-cured cases were observed in Ei-CVPTC with respect to Ei-FVPTC, but not in En-CVPTC to En-FVPTC. Multivariate clustering analysis showed that En-FVPTC, En-CVPTC, and Ei-FVPTC have similar features but different from I-FVPTC and I-CVPTC and, to a lesser extent, from Ei-CVPTC. A total of 177 of 614 (28.8%) cases were BRAFV600E mutated, and 10 of 614 (1.6%) carried BRAF-rare alterations. A significantly higher rate of En-CVPTC (22/49, 44.9%) than En-FVPTC (15/195, 7.7%) (P < .0001) were BRAFV600E mutated. CONCLUSION: En-CVPTC is less prevalent than En-FVPTC. However, it has good clinical/ pathological behavior comparable to En-FVPTC. This finding confirms the good prognostic role of a whole tumor capsule in CVPTC as well. New nomenclature for En-CVPTC, similar to that introduced for En-FVPTC (ie, noninvasive follicular thyroid neoplasm with papillary-like nuclear features; NIFTP) could be envisaged.

Struma ovarii and peritoneal strumosis during pregnancy.

BACKGROUND: Struma ovarii is a special type of ovarian dermoid cyst and accounts for approximately 2-3 % of all dermoid tumours. Benign struma ovarii may manifest as distant metastasis, called peritoneal strumosis, which makes it biologically similar to malignancy, and has been reported in limited cases but never discovered during pregnancy. CASE PRESENTATION: We report a patient with a history of right struma ovarii cystectomy. During pregnancy, pelvic masses with non-specific clinical presentation were found again. During the caesarean section, contralateral struma ovarii with dissemination of nodules in the peritoneal cavity was found, and pathology revealed that the masses were thyroid follicle ovarian goitres. DISCUSSION AND CONCLUSIONS: Recurrent benign struma ovarii with extraovarian dissemination is a rare aggressive clinical manifestation different from malignancy. It is emphasized that adequate assessment and complete resection of suspicious masses are of great importance.

Clinicopathologic Characteristics of Thyroid Nodules Positive for the THADA-IGF2BP3 Fusion on Preoperative Molecular Analysis.

Background: Thyroid adenoma-associated (THADA)-IGF2BP3 fusions have been identified as an oncogenic event in thyroid neoplasms. However, the prevalence of this gene fusion and associated phenotypical and clinical features are not well defined. The aim of this study was to characterize thyroid nodules positive for THADA-IGF2BP3 fusions on preoperative molecular analysis, review surgical outcomes, and explore potential impact of the fusion detection on patient management. Methods: Thyroid nodules positive for THADA-IGF2BP3 fusion on ThyroSeq v3 genomic classifier (GC) testing of fine needle aspiration (FNA) (n = 30) samples from November 2017 to August 2019 were identified. Demographic and clinical data were obtained by retrospective chart review; pathology slides were re-examined. Results: Thirty nodules positive for THADA-IGF2BP3 fusion on FNA were identified, representing ∼2% of 1280 nodules that underwent molecular analysis. Of the 27 nodules with available cytology diagnosis data, 22 (81%) were diagnosed as atypia of undetermined significance, 3 (11%) as follicular neoplasm, and 1 (4%) each were benign, and suspicious for malignancy. No additional mutations or gene fusions were identified in any of the nodules. Of the 24 cases with available clinical data, 22 (92%) THADA-IGF2BP3-positive nodules were managed surgically, 14 (64%) by thyroid lobectomy, and 8 (36%) by total thyroidectomy. Of the patients who had initial lobectomy, 3 (21%) had completion surgery. On surgical pathology, 7 (32%) THADA-IGF2BP3-positive nodules were malignant (six encapsulated follicular variant papillary thyroid carcinomas (EFVPTC), one minimally infiltrative FVPTC), 10 (45%) noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and 5 (23%) follicular adenomas (FA). THADA-IGF2BP3-positive malignancies were intrathyroidal, without aggressive histology. Nodule size was similar between malignant nodules, NIFTP, and FA (2.6, 2.7, and 2.3 cm, respectively; p = 0.77). On limited follow-up (mean, 18 months) available for six patients with malignant fusion-positive nodule and 4 patients with NIFTP, no tumor recurrences were found. Conclusions: In this series of patients, 77% of THADA-IGF2BP3 fusion-positive thyroid nodules were thyroid tumors requiring surgery, either papillary carcinoma or NIFTP. However, all cancers were low risk, predominantly encapsulated FVPTCs and thus can likely be adequately treated with lobectomy.

Analysis of Malignant Thyroid Nodules That Do Not Meet ACR TI-RADS Criteria for Fine-Needle Aspiration.

OBJECTIVE. Compared with other guidelines, the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) has decreased the number of nodules for which fine-needle aspiration is recommended. The purpose of this study was to evaluate the characteristics of malignant nodules that would not be biopsied when the ACR TI-RADS recommendations are followed. MATERIALS AND METHODS. We retrospectively reviewed a total of 3422 thyroid nodules for which a definitive cytologic diagnosis, a definitive histologic diagnosis, or both diagnoses as well as diagnostic ultrasound (US) examinations were available. All nodules were categorized using the ACR TI-RADS, and they were divided into three groups according to the recommendation received: fine-needle aspiration (group 1), follow-up US examination (group 2), or no further evaluation (group 3). RESULTS. Of the 3422 nodules, 352 were malignant. Of these, 240 nodules were assigned to group 1, whereas 72 were assigned to group 2 and 40 were included in group 3. Sixteen of the 40 malignant nodules in group 3 were 1 cm or larger, and, on the basis of analysis of the sonographic features described in the ACR TI-RADS, these nodules were classified as having one of five ACR TI-RADS risk levels (TR1-TR5), with one nodule classified as a TR1 nodule, eight as TR2 nodules, and seven as TR3 nodules. If the current recommendation of no follow-up for TR2 nodules was changed to follow-up for nodules 2.5 cm or larger, seven additional malignant nodules and 316 additional benign nodules would receive a recommendation for follow-up. If the current size threshold (1.5 cm) used to recommend US follow-up for TR3 nodules was decreased to 1.0 cm, seven additional malignant nodules and 118 additional benign nodules would receive a recommendation for follow-up. CONCLUSION. With use of the ACR TI-RADS, most malignant nodules that would not be biopsied would undergo US follow-up, would be smaller than 1 cm, or would both undergo US follow-up and be smaller than 1 cm. Adjusting size thresholds to decrease the number of missed malignant nodules that are 1 cm or larger would result in a substantial increase in the number of benign nodules undergoing follow-up.

Deep learning prediction of BRAF-RAS gene expression signature identifies noninvasive follicular thyroid neoplasms with papillary-like nuclear features.

Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are follicular-patterned thyroid neoplasms defined by nuclear atypia and indolent behavior. They harbor RAS mutations, rather than BRAFV600E mutations as is observed in papillary thyroid carcinomas with extensive follicular growth. Reliably identifying NIFTPs aids in safe therapy de-escalation, but has proven to be challenging due to interobserver variability and morphologic heterogeneity. The genomic scoring system BRS (BRAF-RAS score) was developed to quantify the extent to which a tumor's expression profile resembles a BRAFV600E or RAS-mutant neoplasm. We proposed that deep learning prediction of BRS could differentiate NIFTP from other follicular-patterned neoplasms. A deep learning model was trained on slides from a dataset of 115 thyroid neoplasms to predict tumor subtype (NIFTP, PTC-EFG, or classic PTC), and was used to generate predictions for 497 thyroid neoplasms within The Cancer Genome Atlas (TCGA). Within follicular-patterned neoplasms, tumors with positive BRS (RAS-like) were 8.5 times as likely to carry an NIFTP prediction than tumors with negative BRS (89.7% vs 10.5%, P < 0.0001). To test the hypothesis that BRS may serve as a surrogate for biological processes that determine tumor subtype, a separate model was trained on TCGA slides to predict BRS as a linear outcome. This model performed well in cross-validation on the training set (R2 = 0.67, dichotomized AUC = 0.94). In our internal cohort, NIFTPs were near universally predicted to have RAS-like BRS; as a sole discriminator of NIFTP status, predicted BRS performed with an AUC of 0.99 globally and 0.97 when restricted to follicular-patterned neoplasms. BRAFV600E-mutant PTC-EFG had BRAFV600E-like predicted BRS (mean -0.49), nonmutant PTC-EFG had more intermediate predicted BRS (mean -0.17), and NIFTP had RAS-like BRS (mean 0.35; P < 0.0001). In summary, histologic features associated with the BRAF-RAS gene expression spectrum are detectable by deep learning and can aid in distinguishing indolent NIFTP from PTCs.

Long-term follow-up of differentiated thyroid carcinoma in children and adolescents.

Objectives The aims were to analyze the clinical features, response to treatment, prognostic factors and long-term follow-up of children and adolescents with differentiated thyroid carcinoma (DTC). Methods Eighty patients with DTC were studied retrospectively. All underwent total or near-total thyroidectomy, and in 75 cases, ablative iodine therapy was recommended. Patients were assessed periodically by tests for serum thyroglobulin levels and whole-body iodine scans. Age, gender, initial clinical presentation, histology, tumor stage, postoperative complications, radioiodine treatment protocol, treatment response, thyroglobulin (Tg), recurrence and long-term disease progression were evaluated. Results Seventy patients completed >2 years of follow-up (23 males, 47 females; median age: 14 years; range: 3-18 years). Sixty-two patients showed papillary DTC and eight, follicular DTC. Sixty-five percent presented nodal metastasis and 16%, pulmonary metastasis at diagnosis. Six months after first radioiodine treatment, 36.2% of patients were free of disease. Seven recurrences were documented. At the end of follow-up, overall survival was 100%, and 87.2% of patients were in complete remission. Nine patients had persistent disease. We found a significant association between stage 4 and persistent disease. Hundred percent of patients with negative Tg values at 6 months posttreatment were documented free of disease at the end of the follow-up. The analysis of disease-free survival based on radioiodine treatment protocols used showed no statistically significant differences. Conclusions DTC in children and adolescents is frequently associated with presence of advanced disease at diagnosis. Despite this, complete remission was documented after treatment in most cases, with a good prognosis in the long-term follow-up. Negative posttreatment thyroglobulin and stage 4 at diagnosis were significant prognostic variables.

Characterization of pathological thyroid tissue using polarization-sensitive second harmonic generation microscopy.

Polarization-sensitive second harmonic generation (SHG) microscopy is an established imaging technique able to provide information related to specific molecular structures including collagen. In this investigation, polarization-sensitive SHG microscopy was used to investigate changes in the collagen ultrastructure between histopathology slides of normal and diseased human thyroid tissues including follicular nodular disease, Grave's disease, follicular variant of papillary thyroid carcinoma, classical papillary thyroid carcinoma, insular or poorly differentiated carcinoma, and anaplastic or undifferentiated carcinoma ex vivo. The second-order nonlinear optical susceptibility tensor component ratios, χ(2)zzz'/χ(2)zxx' and χ(2)xyz'/χ(2)zxx', were obtained, where χ(2)zzz'/χ(2)zxx' is a structural parameter and χ(2)xyz'/χ(2)zxx' is a measure of the chirality of the collagen fibers. Furthermore, the degree of linear polarization (DOLP) of the SHG signal was measured. A statistically significant increase in χ(2)zzz'/χ(2)zxx' values for all the diseased tissues except insular carcinoma and a statistically significant decrease in DOLP for all the diseased tissues were observed compared to normal thyroid. This finding indicates a higher ultrastructural disorder in diseased collagen and provides an innovative approach to discriminate between normal and diseased thyroid tissues that is complementary to standard histopathology.

Molecular Profiling of Follicular Variant of Papillary Thyroid Cancer.

The molecular features of the follicular variant of papillary thyroid cancer are closely related to the clinical behavior of the tumor and the prognosis of the disease. BRAF-V600E mutations in patients with a follicular variant of papillary thyroid cancer have not been identified; however, the majority of patients had T3-4N0M0 stage of the disease. Changes in the expression of transcription and growth factors and AKT/m-TOR signaling pathway components were detected. In addition, hyperexpression of m-TOR and 4EBP1 kinases and CAIX enzyme was shown compared to the classical variant of papillary thyroid cancer, where an increase in the nuclear factor NF-κB p65 and c-RAF kinase expression was observed.

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21.

Background: The long noncoding RNA (lncRNA) functions as a regulator of initiation, progression, and metastasis of thyroid carcinomas. lncRNA OTUD6B antisense RNA 1 (OTUD6B-AS1) is a tumor-suppressive noncoding RNA in clear cell renal cell carcinoma. The role of OTUD6B-AS1 in thyroid carcinomas has not been reported yet. We aim to investigate the expression and biological functions of OTUD6B-AS1 in thyroid carcinomas. Methods: The expression level of OTUD6B-AS1 was measured in 60 paired human thyroid carcinoma tissues and corresponding adjacent normal thyroid tissues. The correlations between the OTUD6B-AS1 expression levels and clinicopathological features were evaluated using the Mann-Whitney test. The effects of OTUD6B-AS1 on thyroid carcinoma cells were determined via the MTT and transwell assays. The potential targets of OTUD6B-AS1 were screened using the online programs OncomiR and StarBase 3.0, and the LncBase Predicted v.2. Luciferase reporter assay was used to confirm the interactions between OTUD6B-AS1 and its potential targets. Results: OTUD6B-AS1 was downregulated in thyroid carcinoma tissue samples. The expression of OTUD6B-AS1 correlated with tumor size, clinical stage, and lymphatic metastasis of thyroid carcinoma. Overexpression of OTUD6B-AS1 significantly decreased the viability, migration, and invasion of thyroid carcinoma cells. Online programs predicted miR-183-5p and miR-21 as potential targets of OTUD6B-AS1. Luciferase reporter assays showed miR-183-5p and miR-21 bound to OTUD6B-AS1. Moreover, overexpression of miR-183-5p and miR-21 compromised the inhibitory effects of OTUD6B-AS1 on viability, migration, and invasion of thyroid carcinoma cells. Conclusions: Taken together, our findings present in vitro evidence of lncRNA OTUD6B-AS1 as a tumor suppressor in thyroid carcinomas. OTUD6B-AS1 inhibits viability, migration, and invasion of thyroid carcinoma by targeting miR-183-5p and miR-21.

[Hereditary predispositions to follicular thyroid tumors]. / Prédispositions héréditaires aux tumeurs thyroïdiennes de souche folliculaire.

Familial thyroid cancers of follicular origin are rare and include syndromic and non-syndromic tumours. In familial adenomatous polyposis, the prevalence of papillary thyroid cancer is 2-12% and in 20-40% of cases it is a cribriform-morular papillary thyroid carcinoma. Morules and cribriform pattern are the two main typical criteria, associated with a nuclear and cytoplasmic immunopositivity for beta catenin. DICER1 syndrome is associated with pleuropneumoblastoma, ovarian tumors and thyroid pathology (multinodular goiter and less frequently a well-differentiated thyroid cancer without microscopic particularity). Cowden syndrome is characterized by multiple hamartomas and two-thirds of patients develop thyroid pathology, including multinodular goiter (50-67%) and cancer (35%), the latter being one of the major diagnostic criteria of the syndrome. Classic triad of Carney complex associates lentiginosis, myxoid tumors, and various endocrine abnormalities; thyroid pathology occurs in 10% of cases and may be benign or malignant. In Werner's syndrome, thyroid cancer is present in 18% of cases. McCune-Albright syndrome is characterized by fibrous dysplasia, café-au-lait spots and various endocrinopathies including hyperthyroidism and nodular hyperplasia. Non-syndromic thyroid cancers, which represent the majority of familial cancers, are most often papillary carcinomas. In daily practice, in the presence of multiple benign thyroid nodules and/or thyroid cancer in a young person, or with family thyroid diseases, the pathologist should be aware about hereditary predispositions to propose an oncogenetic consultation.

[Tumors of the thyroid gland. Proposal for the management and study of samples from patients with thyroid neoplasms]. / Tumores de la glándula tiroides. Propuesta para el manejo y estudio de las muestras de pacientes con neoplasias tiroideas.

The recent changes in the classification and staging of thyroid tumors have arisen from the need to provide an adequate response to the exponential increase of thyroid cancer, which, however, has not been accompanied by an increase in mortality. These changes pretend to reduce overdiagnoses of malignancy, unnecessary treatment, side effects as well as cost for the health system. To this end, this article reviews recommendations for the management of thyroid surgical pathology samples with emphasis on the new terminology of the WHO classification. The basic criteria for the diagnosis of malignancy in well-differentiated thyroid carcinomas are reviewed and the criteria for NIFTP (non-invasive follicular tumor with papillary-like nuclear features) diagnosis are updated. Recommendations for the elaboration of the pathological report are also included.

Molecular Profile and Clinicopathologic Features of Follicular Variant Papillary Thyroid Carcinoma.

The non-invasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has an indolent clinical behavior. Recently, it was proposed that this tumor type should be reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). To characterize NIFTPs, we evaluated the molecular and clinicopathologic characteristics of each FVPTC subtype. This study enrolled 29 patients with FVPTC who underwent thyroidectomy between January 2007 and June 2017. They were classified as non-invasive encapsulated FVPTC (NIFTP, n = 10), invasive encapsulated FVPTC (n = 11), and infiltrative FVPTC (n = 8) by two independent pathologists. Genetic alterations were analyzed by targeted next-generation sequencing using formalin-fixed, paraffin-embedded tissue samples and the clinicopathologic characteristics were retrospectively reviewed. There was no difference in preoperative cytologic classification between NIFTPs and invasive encapsulated FVPTCs, whereas infiltrative FVPTC was more likely to be Bethesda class VI than the encapsulated type (50% versus 9.5%; P = 0.033). Lymph node metastasis was not found in NIFTPs. There was no BRAFV600E mutation in NIFTPs, whereas one of 11 invasive encapsulated FVPTCs and three of 8 infiltrative FVPTCs harbored BRAFV600E. RAS mutations were frequently detected in encapsulated FVPTCs (5 of 10 NIFTPs and 4 of 11 invasive encapsulated FVPTCs) but were only detected in one case of the infiltrative type. There were no differences in molecular or clinicopathologic profiles between non-invasive and invasive encapsulated FVPTCs, except for lymph node metastasis and the presence of BRAFV600E. NIFTP has favorable pathologic characteristics with a high frequency of RAS mutations.